Supritha Dugyala1, Travis S Ptacek2,3, Jeremy M Simon2,3,4, Yuhui Li5, Flavio Fröhlich6,7,8,9,10,11. 1. Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. 2. UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA. 3. Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA. 4. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA. 5. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. 6. UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA. flavio_frohlich@med.unc.edu. 7. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. flavio_frohlich@med.unc.edu. 8. Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. flavio_frohlich@med.unc.edu. 9. Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. flavio_frohlich@med.unc.edu. 10. Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. flavio_frohlich@med.unc.edu. 11. Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 115 Mason Farm Rd. NRB 4109F, Chapel Hill, NC, 27599, USA. flavio_frohlich@med.unc.edu.
Abstract
BACKGROUND: Increasing evidence suggests a causal relationship between the gut microbiome and psychiatric illnesses. In particular, autism spectrum disorder is associated with gastrointestinal symptoms and alterations in the gut microbiome. Administration of probiotics is a commonly used strategy by caregivers of people with neurodevelopmental illness. However, evidence for successful improvement in gut microbiome and (behavioral) symptoms has been lacking. RESULTS: Here, we use a novel ferret model of maternal immune activation to show that high-dose probiotic administration in a placebo-controlled study design causes changes in the gut microbiome in the form of a transient increase in the administered bacterial species. In contrast, we found no differences in baseline microbiome composition or changes induced by probiotic administration between animals exposed in utero to maternal immune activation and control animals. However, the relative presence of several bacterial species correlated with an increased preference for novelty (object and conspecific). Intriguingly, several of the hits in this screen are species that have previously emerged in the literature as being associated with autism and anxiety. CONCLUSIONS: Together, our results suggest that high-dose probiotic interventions may be beneficial for the adjunct treatment of psychiatric illnesses. Placebo-controlled clinical trials in humans are urgently needed.
BACKGROUND: Increasing evidence suggests a causal relationship between the gut microbiome and psychiatric illnesses. In particular, autism spectrum disorder is associated with gastrointestinal symptoms and alterations in the gut microbiome. Administration of probiotics is a commonly used strategy by caregivers of people with neurodevelopmental illness. However, evidence for successful improvement in gut microbiome and (behavioral) symptoms has been lacking. RESULTS: Here, we use a novel ferret model of maternal immune activation to show that high-dose probiotic administration in a placebo-controlled study design causes changes in the gut microbiome in the form of a transient increase in the administered bacterial species. In contrast, we found no differences in baseline microbiome composition or changes induced by probiotic administration between animals exposed in utero to maternal immune activation and control animals. However, the relative presence of several bacterial species correlated with an increased preference for novelty (object and conspecific). Intriguingly, several of the hits in this screen are species that have previously emerged in the literature as being associated with autism and anxiety. CONCLUSIONS: Together, our results suggest that high-dose probiotic interventions may be beneficial for the adjunct treatment of psychiatric illnesses. Placebo-controlled clinical trials in humans are urgently needed.
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